Potassium Phosphate, Tribasic → 4-(2-aminophenyl)-5-(3-benzenesulfonylpropyl)-1-butyl-1H-pyrazole-3-carbonitrile

HRID 1360551

Reaction equation

HRID 1360551 reaction equation
Cl.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:20]1([S:26]([CH2:29][CH2:30][CH2:31][C:32]2[N:36]([CH2:37][CH2:38][CH2:39][CH3:40])[N:35]=[C:34]([C:41]#[N:42])[C:33]=2Br)(=[O:28])=[O:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:33]1[C:34]([C:41]#[N:42])=[N:35][N:36]([CH2:37][CH2:38][CH2:39][CH3:40])[C:32]=1[CH2:31][CH2:30][CH2:29][S:26]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)(=[O:28])=[O:27]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 164270902-Aminophenylboronic acid hydrochlorideHCID 669585995-(3-benzenesulfonylpropyl)4-bromo-1-butyl-1H-pyrazole-3-carbonitrile

Product 1

HCID 669588264-(2-aminophenyl)-5-(3-benzenesulfonylpropyl)-1-butyl-1H-pyrazole-3-carbonitrileYield 100.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

2-Aminophenyl boronic acid hydrochloride (693 mg, 4.00 mmol) and potassium phosphate tribasic (2.12 g, 10.0 mmol) were added sequentially to a solution of 5-(3-benzenesulfonylpropyl)-4-bromo-1-butyl-1H-pyrazole-3-carbonitrile (550 mg, 1.30 mmol) in 15 mL of toluene in a pressure tube. Nitrogen was bubbled through the resultant slurry for 15 minutes. Tris(dibenzylideneacetone)dipalladium(0) (104 mg, 0.10 mmol), bis[(2-diphenylphosphino)phenyl]ether (65 mg, 0.12 mmol), and 4 angstrom molecular sieves were then added to the reaction mixture. The pressure tube was sealed and heated in a 110° C. oil bath. After 20 hours, the reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and filtered through CELITE filter aid. The filtrate was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The aqueous layer was extracted with additional ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated to an orange oil. Purification via flash column chromatography on silica gel (eluting with hexane:ethyl acetate in a gradient from 2:1 to 2:3) afforded 550 mg of 4-(2-aminophenyl)-5-(3-benzenesulfonylpropyl)-1-butyl-1H-pyrazole-3-carbonitrile as a thick pale yellow oil.

Workup

  1. customNitrogen was bubbled through the resultant slurry for 15 minutes
  2. customThe pressure tube was sealed
  3. temperaturethe reaction mixture was cooled to ambient temperature
  4. filtrationfiltered through CELITE
  5. filtrationfilter aid
  6. additionThe filtrate was diluted with ethyl acetate
  7. washwashed with saturated aqueous sodium bicarbonate
  8. extractionThe aqueous layer was extracted with additional ethyl acetate
  9. washthe combined organic layers were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to an orange oil
  13. customPurification via flash column chromatography on silica gel (
  14. washeluting with hexane

Sources & evidence

ORD record
ord-f9703a39462f40ecb80f2b571ec46514
Source dataset
uspto-grants-2011_02
Patent number
US07879849B2

Linked notes

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